tbuckley/cabot-search huggingface dataset:
Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study
Authors: Jurjen Versluis, Wael Saber, Harrison K. Tsai, Christopher J. Gibson, Laura W. Dillon, Asmita Mishra, Joseph McGuirk, Richard T. Maziarz, Peter Westervelt, Pranay Hegde, Devdeep Mukherjee, Michael J. Martens, Brent Logan, Mary Horowitz, Christopher S. Hourigan, Ryotaro Nakamura, Corey Cutler, R. Coleman Lindsley
Journal: Journal of Clinical Oncology (2023)

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. METHODS We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53 multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity). RESULTS The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P &lt; .001). Among those with a TP53 mutation, OS was similar between TP53 single versus TP53 multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P &lt; .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001). CONCLUSION HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.
Genomic Profiling Reveals Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma
Authors: Diana Mandelker, Antonio Marra, Binbin Zheng-Lin, Pier Selenica, Juan Blanco-Heredia, Yingjie Zhu, Andrea Gazzo, Donna Wong, Zarina Yelskaya, Vikas Rai, Joshua Somar, Silvana Ostafi, Nikita Mehta, Ciyu Yang, Yirong Li, David N. Brown, Edaise M. da Silva, Xin Pei, Irina Linkov, Panieh Terraf, Maksym Misyura, Ozge Ceyhan-Birsoy, Marc Ladanyi, Michael Berger, Fresia Pareja, Zsofia Stadler, Kenneth Offit, Nadeem Riaz, Wungki Park, Joanne Chou, Marinela Capanu, Maria Koehler, Ezra Rosen, Eileen M. O'Reilly, Jorge S. Reis-Filho
Journal: Journal of Clinical Oncology (2023)

PURPOSE To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features. METHODS Both somatic and germline analyses were performed using an Food and Drug Administration–authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 of whom were diagnosed with PACC. For a subset of PACCs, whole-genome sequencing (WGS; n = 12) and RNA sequencing (n = 6) were performed. RESULTS Eighteen of 49 (36.7%) PACCs harbored germline pathogenic variants in homologous recombination (HR) and DNA damage response (DDR) genes, including BRCA1 (n = 1), BRCA2 (n = 12), PALB2 (n = 2), ATM (n = 2), and CHEK2 (n = 1). Thirty-one PACCs displayed pure, and 18 PACCs harbored mixed acinar cell histology. Fifteen of 31 (48%) pure PACCs harbored a germline pathogenic variant affecting HR-/DDR-related genes. BRCA2 germline pathogenic variants (11 of 31, 35%) were significantly more frequent in pure PACCs than in pancreatic adenocarcinoma (86 of 2,739, 3.1%; P &lt; .001), high-grade serous ovarian carcinoma (67 of 1,318, 5.1%; P &lt; .001), prostate cancer (116 of 3,401, 3.4%; P &lt; .001), and breast cancer (79 of 3,196, 2.5%; P &lt; .001). Genomic features of HR deficiency (HRD) were detected in 7 of 12 PACCs undergoing WGS, including 100% (n = 6) of PACCs with germline HR-related pathogenic mutations and 1 of 6 PACCs lacking known pathogenic alterations in HR-related genes. Exploratory analyses revealed that in PACCs, the repertoire of somatic driver genetic alterations and the load of neoantigens with high binding affinity varied according to the presence of germline pathogenic alterations affecting HR-/DDR-related genes and/or HRD. CONCLUSION In a large pan-cancer cohort, PACC was identified as the cancer type with the highest prevalence of both BRCA2 germline pathogenic variants and genomic features of HRD, suggesting that PACC should be considered as part of the spectrum of BRCA-related malignancies.
De Novo Oligometastatic Breast Cancer
Authors: Lajos Pusztai, Mariya Rozenblit, Peter Dubsky, Thomas Bachelot, Anna M. Kirby, Barbro K. Linderholm, Julia R. White, Steven J. Chmura, Lisa A. Carey, Boon H. Chua, Kathy D. Miller
Journal: Journal of Clinical Oncology (2023)

De novo oligometastatic breast cancer, a unique disease needing new treatment paradigms.
Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function
Authors: Kevan C. Herold, Stephen E. Gitelman, Peter A. Gottlieb, Laura A. Knecht, Ralph Raymond, Eleanor L. Ramos
Journal: Diabetes Care (2023)

OBJECTIVE In November 2022, teplizumab-mzwv became the first drug approved to delay the onset of stage 3 type 1 diabetes in adults and children age ≥8 years with stage 2 type 1 diabetes on the basis of data from the pivotal study TN-10. RESEARCH DESIGN AND METHODS To provide confirmatory evidence of the effects of teplizumab on preserving endogenous insulin production, an integrated analysis of C-peptide data from 609 patients (n = 375 patients receiving teplizumab and n = 234 control patients) from five clinical trials in stage 3 type 1 diabetes was conducted. RESULTS The primary outcome of the integrated analysis, change from baseline in stimulated C-peptide, was significantly improved at years 1 (average increase 0.08 nmol/L; P &amp;lt; 0.0001) and 2 (average increase 0.12 nmol/L; P &amp;lt; 0.0001) after one or two courses of teplizumab. An analysis of exogenous insulin use was also conducted, showing overall reductions of 0.08 (P = 0.0001) and 0.10 units/kg/day (P &amp;lt; 0.0001) at years 1 and 2, respectively. An integrated safety analysis of five clinical trials that enrolled 1,018 patients with stage 2 or 3 type 1 diabetes (∼1,500 patient-years of follow-up for teplizumab-treated patients) was conducted. CONCLUSIONS These data confirm consistency in the preservation of β-cell function, as measured by C-peptide, across multiple clinical trials. This analysis showed that the most common adverse events included lymphopenia, rash, and headache, a majority of which occurred during and after the first few weeks of teplizumab administration and generally resolved without intervention, consistent with a safety profile characterized by self-limited adverse events after one or two courses of teplizumab treatment.
Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties
Authors: Ying Chen, Xing Wang, Sheng Tao, Qi Wang, Pan-Qin Ma, Zi-Biao Li, Yun-Long Wu, Da-Wei Li
Journal: Military Medical Research (2023)

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem. Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity, good drug-loading ability and sustained drug release properties. As a typical example, hyaluronic acid dressing (Healoderm) has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers. However, the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment. Due to the intricacy of diabetic wounds, antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice, although these medications are easily hindered by the hostile environment. In this case, scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds (such as high glucose and low pH) or combined with external stimuli (such as light or magnetic field) to achieve controllable drug release, gel degradation, and microenvironment improvements in order to overcome these clinical issues. These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings. Here, we review recent advances on responsive-hydrogel dressings towards diabetic wound healing, with focus on hydrogel structure design, the principle of responsiveness, and the behavior of degradation. Last but not least, the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed. We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.
Prediction of outcomes in patients with acute variceal bleeding
Authors: Ian A. Rowe
Journal: Hepatology (2023)

Associate Professor and Honorary Consultant Hepatologist, Leeds Institute for Medical Research, University of Leeds & Leeds Liver Unit, St James's University Hospital Correspondence Ian A. Rowe, Room 6.1 Clinical Sciences Building, St James's University Hospital, Leeds, LS9 7TF, UK. Email: [email protected]
Geospatial analysis of cyanobacterial exposure and liver cancer in the contiguous United States
Authors: Matthew Ledenko, Samuel O. Antwi, Tushar Patel
Journal: Hepatology (2023)

Background and Aims: Cyanobacteria are commonly found in water bodies and their production of hepatotoxins can contribute to liver damage. However, the population health effects of cyanobacteria exposure (CE) are unknown. Our objectives were to determine the effect of chronic exposure to cyanobacteria through proximity to water bodies with high cyanobacteria counts on the incidence and mortality of liver cancers, as well as to identify location-based risk factors. Approach and Results: Across the contiguous United States, regions with high cyanobacteria counts in water bodies were identified using satellite remote sensing data. The data were geospatially mapped to county boundaries, and disease mortality and incidence rates were analyzed. Distinctive spatial clusters of CE and mortality related to liver diseases or cancer were identified. There was a highly significant spatial association between CE, liver disease, and liver cancer but not between CE and all cancers. Hot spots of CE and mortality were identified along the Gulf of Mexico, eastern Texas, Louisiana, and Florida, and cold spots across the Appalachians. The social vulnerability index was identified as a major location-based determinant by logistic regression, with counties in the fourth or fifth quintiles having the highest prevalence of hot spots of CE and mortality from liver cancer. Conclusions: These findings emphasize the importance of environmental exposure to cyanobacteria as a location-based determinant of mortality from liver cancer. Public health initiatives addressing CE may be considered to reduce mortality, particularly in areas of high social vulnerability.
Dual elastography to discriminate adjacent stages of fibrosis and inflammation in chronic hepatitis B: A prospective multicenter study
Authors: Dou Jianping, Chen Xi, Cheng Guangwen, Meng Fankun, Zheng Ying, Zhang Bulin, Zhang Wei, Zhang Yao, Yin Zhiyong, Yang Hong, Lin Peng, Li Jiaping, Chen Zheng, Wei Shujing, Xu Xiting, Chen Chengcai, Chen Biwu, Huang Xuning, Fan Huiwen, Wu Jing, Zhu Jiabao, Xie Yuhuan, Lu Jingxin, Ding Hong, Liang Ping, Yu Jie
Journal: Hepatology (2023)

Background and Aims: To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV. Approach and Results: Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p &lt; 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis. Conclusions: Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.
P1317: TIME-DEPENDENT ANALYSIS OF THE IMPACT ON EARLY CMV REACTIVATION OF HLA MISMATCH AND ACUTE GRAFT-VERSUS-HOST-DISEASE AFTER ALLO-HSCT FROM RELATED DONORS IN ACQUIRED APLASTIC ANEMIA.
Authors: Fan Lin, Xinyu Dong, Yuan-Yuan Zhang, Yifei Cheng, Tingting Han, Xiao-Dong Mo, Haixia Fu, Wei Han, Fengrong Wang, Feifei Tang, Chen-Hua Yan, Yuqian Sun, Zhengli Xu, Yu Wang, Xiao-Hui Zhang, Xiao-Jun Huang, Lanping Xu
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Cytomegalovirus (CMV) reactivation is an important issue in allogeneic hematopoietic cell transplantation (HCT). Studies have found higher incidences of CMV reactivation in HLA-mismatched HCT compared to HLA-matched transplants. Particularly, the high incidence of acute graft-versus-host disease (aGvHD) in HLA-mismatched transplants is known to be a significant risk factor for CMV reactivation. It is undetermined whether the degree of HLA mismatch is associated with CMV reactivation. Aims: To comprehensively evaluate the association between HLA mismatch and GvHD and early CMV reactivation. Moreover, we try to determine the impact of HLA mismatch independent of GvHD. Methods: We retrospectively analyzed 355 patients with acquired aplastic anemia who received related donor transplants using a unified antithymocyte globulin-based platform. Patients were divided into group 1 (6/6 HLA match), group 2 (1-2/6 HLA allelic mismatch), and group 3 (3/6 HLA allelic mismatch). The impact of covariates was analyzed through two models: (1) time- dependent Cox, and (2) dynamic landmarking analysis. Results: The time-dependent Cox model showed that the HLA mismatch of 3/6 alleles [hazard ratio (HR) =1.852, P =.004] and aGvHD (HR = 1.009, P=.019) were independent risk factors for CMV reactivation. With the dynamic landmarking analysis, a higher HLA disparity corelated to increased early CMV reactivation (HR = 1.606, P =.001) at all time points. Developing aGvHD following HCT was generally associated with a higher incidence of CMV reactivation (HR = 1.623, P =.013). Its impact varied with time and was greater at earlier landmark timepoints. Specifically, aGvHD by the 20-day (P <.001), 30-day (P <.001), 40-day (P =.012), and 50-day (P =.032) landmark time points were associated with CMV reactivation. The risk of CMV reactivation for aGvHD patients decreased with successive later landmark time points (P >.05). Summary/Conclusion: Conclusively, our data suggest that the higher degree of HLA disparity and the occurrence of aGvHD increases susceptibility to early CMV reactivation. In particular, the dynamic landmarking analysis demonstrated the time-varying effect of aGvHD on CMV reactivation. HLA mismatch showed a profound impact on CMV reactivation over time following HCT.figure 1figure 2 Keywords: Cytomegalovirus, HLA, Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant
The ecological importance of hybridization
Authors: Daniele Porretta, Daniele Canestrelli
Journal: Trends in Ecology & Evolution (2023)

Hybridization as an evolutionary process has been studied in depth over the past few decades. Research has focused on its role in shaping reproductive barriers, its adaptive value, and its genomic consequences. In contrast, our knowledge of ecological dimensions of hybridization is still in its infancy, despite hybridization being an inherently ecological interaction. Using examples from various organisms, we show that hybridization can affect and be affected by non-reproductive interactions, including predation, competition, parasitism, mutualism, commensalism, and organism–environment interactions, with significant implications for community structure and ecosystem functioning. However, since these dimensions of hybridization have mostly been revealed from studies designed to decipher other evolutionary processes, we argue that much of the eco-evolutionary importance of hybridization is yet to be discovered.
P1546: HEMATOLOGIC ADVERSE EVENTS AFTER COVID-19 VACCINATION IN THE PHILIPPINES: A NATIONAL DATABASE STUDY
Authors: Flordeluna Mesina, Charles Eryll Sy, Sapinoso Frances Alexandra, Joy Ann De Castro, Preeti Prer Vaswani, Rizza Ann Oquendo, Mark Ryann Lirasan
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Vaccination is regarded as the most important strategy in preventing COVID-19. Vaccine efficacy and safety have been established in clinical trials but real-world data are useful to determine occurrence of adverse events in a population with heterogeneous characteristics. Knowledge on the hematologic events associated with different COVID- 19 vaccines would be beneficial for patients as well as hematologists who oversee the care of these patients. Aims: This study aims to determine the incidence and outcome of hematologic adverse events after COVID-19 vaccination in the Philippines. Methods: This is a cross sectional quantitative study design. Results: There were 268 individuals reported to have hematologic adverse events. Most received Comirnaty at 29.85%. Majority (62.31%) reported hematologic adverse events following the first dose of vaccine. The overall incidence is 0.0182 per 10,000 vaccine doses; lymphadenopathy was the most common hematologic adverse effect with an incidence of 0.011 per 10,000 vaccine doses, followed by anemia at 0.0034 per 10,000 vaccine doses and thrombocytopenia at 0.0017 per 10,000 vaccine doses. Twenty one cases expired with mortality rate at 0.0014 per 10,000 vaccine doses. One-hundred thirty two (49.25%) are fully recovered and 23.88% are recovering from hematologic adverse events as of the time of writing. Summary/Conclusion: The study showed a low incidence of hematologic adverse events reported post COVID- 19 vaccination. The most common abnormality is lymphadenopathy followed by anemia and thrombocytopenia. Autoimmune cytopenias were also reported. Adverse events were more common in the Comirnaty vaccine and after the primary vaccine dose. Majority responded favorably to supportive and/or immunosuppressive therapy using steroids.Keywords: Adverse reaction, Vaccination, COVID-19
P1184: INTERIM DELTASUVMAX CAN IDENTIFY PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA WITH A HIGH RISK OF PRIMARY REFRACTORY DISEASE CANDIDATES FOR EARLY CART COLLECTION
Authors: Carolina Feres, Leonardo Arcuri, Guilherme Neto, Felipe Carvalhaes, Carolina Pereira, Larissa Teixeira, Nelson Hamerschlak, Perini Guilherme
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Up to one-third of patients with diffuse large B-cell lymphoma (DLBCL) fail frontline chemotherapy or have an early relapse, defined as relapse in 12 months. Patients failing to achieve a response after initial therapy have poor outcomes. Accurate prognostication is essential for guiding clinical decision-making and tailoring individual treatment strategies Aims: The objectives of the present study were to determine the prognostic value of early metabolic response in interim PET/CT, analyzed by Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax) criteria, in patients with newly diagnosed DLBCL treated with R-CHOP, and to assess whether the early metabolic response can improve the IPI score accuracy. Methods: This is a retrospective study that included 2 centers. Interim PET-CT was performed after 2-4 cycles of R-CHOP. ΔSUV max was tested as a continuous and categorical variable. The maximally selected rank statistics defined the best cut-off for ΔSUV max (0.77). Results: With a median follow-up of 2.3 years, 112 patients were included. The two-year overall survival was lower for patients with an interim ΔSUV max <0.77 (58% vs 94%, p < 0.001) and for patients with an interim DS of 4 or 5 (65% vs 93%, p < 0.001). Inferior progression-free survival was also observed in the interim ΔSUV max <0.77 group and DS 4-5. The relapse rate was higher for patients with an interim ΔSUVmax<0.77 together with an interim Deauville score of 4 or 5 compared to patients in complete metabolic response (68% x 9%, p<0.01). In multivariable analysis, controlled for IPI, Deauville 4 or 5 combined with an ΔSUV max <0.77 was associated with a higher risk of relapse (HR = 8.70, p <0.001). Summary/Conclusion: In summary, we have shown that the interim ΔSUVmax, an objective and reproducible measure, combined with DS can predict inferior outcomes in patients with DLBCL. At present, changing treatment based on interim PET/CT is not recommended outside clinical trials for DLBCL, however, new therapeutic approaches such as bispecific monoclonal antibodies and CAR-T cell therapy could be considered earlier in the time-lime treatment journey.Legend: Neg/Neg refers to interim ΔSUVmax < 0.77 and interim Deauville criteria 1-3; Pos/Pos refers to interim ΔSUVmax ≥ 0.77 and interim Deauville criteria 4-5; discordant results refers to either interim ΔSUVmax ≥ 0.77 or interim Deauville criteria 4-5. Keywords: FDG-PET, DLBCL